tbuckley/cabot-search huggingface dataset:
Changes in Cancer Screening Rates Following a New Cancer Diagnosis in a Primary Care Patient Panel
Authors: Annabel Z. Wang, Michael L. Barnett, Jessica L. Cohen
Journal: JAMA Network Open (2022)

<h3>Importance</h3> Although screenings for breast and colorectal cancer are widely recommended, patient screening rates vary greatly and remain below public health targets, and primary care physicians' (PCPs') counseling and referrals play critical roles in patients' use of cancer screenings. Recent adverse events may influence PCPs' decision-making, but it remains unknown whether cancer screening rates of PCPs' patients change after PCPs are exposed to new cancer diagnoses. <h3>Objective</h3> To investigate whether PCPs' exposures to patients with new diagnoses of breast or colorectal cancer were associated with changes in screening rates for other patients subsequently visiting the affected PCPs. <h3>Design, Setting, and Participants</h3> This cohort study used stacked difference-in-differences analyses of all-payer claims data for New Hampshire and Maine in 2009 to 2015. Participants were PCPs caring for patients. Data analysis was performed from June 2020 to May 2022. <h3>Exposures</h3> New diagnosis of a PCP's patient with breast cancer or colorectal cancer. <h3>Main Outcomes and Measures</h3> Patients' breast and colorectal cancer screening rates within 1 year of a PCP visit. <h3>Results</h3> The sample included 3158 PCPs (1819 male PCPs [57.6%]) caring for 1 920 189 patients (1 073 408 female patients [55.9%]; mean [SD] age, 41.0 [21.9] years) aged 18 to 64 years. During the study period, 898 PCPs had a patient with a new diagnosis of breast cancer and 370 PCPs had a patient with a new diagnosis of colorectal cancer. In the preexposure period, 68 837 female patients (37.3% of those visiting a PCP) underwent breast cancer screening within 1 year of the visit, and 13 137 patients (10.1% of those visiting a PCP) underwent colorectal cancer screening within 1 year of the visit. For both cancer types, after exposure to a new cancer diagnosis, PCPs' cancer screening rates displayed a rapid, sustained increase. Breast cancer screening rates increased by 4.5 percentage points (95% CI, 3.0-6.1 percentage points;<i>P</i> &lt; .001). Colorectal cancer screening rates increased by 1.3 percentage points (95% CI, 0.3-2.2 percentage points;<i>P</i> = .01). Observed breast cancer screening increases were higher for male PCPs than for female PCPs (3.1 percentage points; 95% CI, 0.4-5.8 percentage points;<i>P</i> = .03). <h3>Conclusions and Relevance</h3> This study found significant, sustained increases in cancer screening rates for patients visiting PCPs recently exposed to new breast and colorectal cancer diagnoses. These findings suggest that PCPs may update practice patterns on the basis of recent patient diagnoses. Future work should assess whether salient cues to PCPs about patient diagnoses when clinically appropriate can improve screening practices.
Identifying and characterising sources of variability in digital outcome measures in Parkinson’s disease
Authors: George Roussos, Teresa Ruiz Herrero, Derek L. Hill, Ariel V. Dowling, Martijn L. T. M. Müller, Luc J. W. Evers, Jackson Burton, Adrian Derungs, Katherine Fisher, Krishna Praneeth Kilambi, Nitin Mehrotra, Roopal Bhatnagar, Sakshi Sardar, Diane Stephenson, Jamie L. Adams, E. Ray Dorsey, Josh Cosman
Journal: npj Digital Medicine (2022)

Abstract Smartphones and wearables are widely recognised as the foundation for novel Digital Health Technologies (DHTs) for the clinical assessment of Parkinson’s disease. Yet, only limited progress has been made towards their regulatory acceptability as effective drug development tools. A key barrier in achieving this goal relates to the influence of a wide range of sources of variability (SoVs) introduced by measurement processes incorporating DHTs, on their ability to detect relevant changes to PD. This paper introduces a conceptual framework to assist clinical research teams investigating a specific Concept of Interest within a particular Context of Use, to identify, characterise, and when possible, mitigate the influence of SoVs. We illustrate how this conceptual framework can be applied in practice through specific examples, including two data-driven case studies.
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Journal: JAMA Network Open (2022)

Quentin Lisan, MD, PhD; Marcel Goldberg, MD, PhD; Ghizlene Lahlou, MD, PhD; Anna Ozguler, MD, PhD; Sylvie Lemonnier, MS; Xavier Jouven, MD, PhD; Marie Zins, MD, PhD; Jean-Philippe Empana, MD, PhD
From the prodromal stage of multiple sclerosis to disease prevention
Authors: Ruth Ann Marrie, Mark Allegretta, Lisa F. Barcellos, Bruce Bebo, Peter A. Calabresi, Jorge Correale, Benjamin Davis, Philip L. De Jager, Christiane Gasperi, Carla Greenbaum, Anne Helme, Bernhard Hemmer, Pamela Kanellis, Walter Kostich, Douglas Landsman, Christine Lebrun-Frenay, Naila Makhani, Kassandra L. Munger, Darin T. Okuda, Daniel Ontaneda, Ronald B. Postuma, Jacqueline A. Quandt, Sharon Roman, Shiv Saidha, Maria Pia Sormani, Jon Strum, Pamela Valentine, Clare Walton, Kathleen M. Zackowski, Yinshan Zhao, Helen Tremlett
Journal: Nature Reviews Neurology (2022)
Selected Articles from This Issue
Journal: Clinical Cancer Research (2022)

Neuroblastoma RAS viral oncogene homolog (NRAS)-mutant melanoma makes up 15%-25% of all melanomas, has a poor prognosis, and has no approved targeted therapies.Enhanced mitogen-activated protein kinase (MAPK) pathway signaling and cell cycle checkpoint dysregulation are characteristic of most NRAS-mutant melanomas.Simultaneous inhibition of MAPK kinase (MEK) and cyclindependent kinase 4/6 (CDK4/6) has shown synergistic antitumor activity in several preclinical models of NRAS-mutant melanoma.The regimen of the MEK inhibitor binimetinib and the selective CDK4/6 inhibitor ribociclib is a rational combination to assess in an NRAS-mutant melanoma population for toxicity and efficacy.In this phase Ib/II study, Schuler and colleagues demonstrate that the combination of ribociclib þ binimetinib achieved target inhibition and tolerability consistent with the known profile of the two agents.Antitumor activity was observed particularly in NRAS-mutant melanomas with concurrent genetic alterations in cell cycle regulators.
Frequent detection of monkeypox virus DNA in saliva, semen, and other clinical samples from 12 patients, Barcelona, Spain, May to June 2022
Authors: Aida Peiró-Mestres, Irene Fuertes, Daniel Camprubí-Ferrer, María Ángeles Marcos, Anna Vilella, Mireia Navarro, Laura Rodriguez-Elena, Josep Riera, Alba Català, Miguel J Martínez, Jose L Blanco
Journal: Eurosurveillance (2022)

A monkeypox (MPX) outbreak has expanded worldwide since May 2022. We tested 147 clinical samples collected at different time points from 12 patients by real-time PCR. MPX DNA was detected in saliva from all cases, sometimes with high viral loads. Other samples were frequently positive: rectal swab (11/12 cases), nasopharyngeal swab (10/12 cases), semen (7/9 cases), urine (9/12 cases) and faeces (8/12 cases). These results improve knowledge on virus shedding and the possible role of bodily fluids in disease transmission.
Early hydroxyurea use is neuroprotective in children with sickle cell anemia
Authors: Kristine Karkoska, Amanda Pfeiffer, Dean W. Beebe, Charles T. Quinn, Omar Niss, Patrick T. McGann
Journal: American Journal of Hematology (2022)

Children with sickle cell disease (SCD) who began hydroyxurea before age five years scored no differently on a measure of cognitive funciton than age, sex, and race-matched unaffected peers.
Current landscape of gene‐editing technology in biomedicine: Applications, advantages, challenges, and perspectives
Authors: Weilin Zhou, Jinrong Yang, Yalan Zhang, Xiaoyi Hu, Wei Wang
Journal: MedComm (2022)

The expanding genome editing toolbox has revolutionized life science research ranging from the bench to the bedside. These "molecular scissors" have offered us unprecedented abilities to manipulate nucleic acid sequences precisely in living cells from diverse species. Continued advances in genome editing exponentially broaden our knowledge of human genetics, epigenetics, molecular biology, and pathology. Currently, gene editing-mediated therapies have led to impressive responses in patients with hematological diseases, including sickle cell disease and thalassemia. With the discovery of more efficient, precise and sophisticated gene-editing tools, more therapeutic gene-editing approaches will enter the clinic to treat various diseases, such as acquired immunodeficiency sydrome (AIDS), hematologic malignancies, and even severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. These initial successes have spurred the further innovation and development of gene-editing technology. In this review, we will introduce the architecture and mechanism of the current gene-editing tools, including clustered regularly interspaced short palindromic repeats (CRISPR) and CRISPR-associated nuclease-based tools and other protein-based DNA targeting systems, and we summarize the meaningful applications of diverse technologies in preclinical studies, focusing on the establishment of disease models and diagnostic techniques. Finally, we provide a comprehensive overview of clinical information using gene-editing therapeutics for treating various human diseases and emphasize the opportunities and challenges.
Epidemiological and microbiological investigation of a large increase in vibriosis, northern Europe, 2018
Authors: Ettore Amato, Maximilian Riess, Daniel Thomas-Lopez, Marius Linkevicius, Tarja Pitkänen, Tomasz Wołkowicz, Jelena Rjabinina, Cecilia Jernberg, Marika Hjertqvist, Emily MacDonald, Jeevan Karloss Antony-Samy, Karsten Dalsgaard Bjerre, Saara Salmenlinna, Kurt Fuursted, Anette Hansen, Umaer Naseer
Journal: Eurosurveillance (2022)

BackgroundVibriosis cases in Northern European countries and countries bordering the Baltic Sea increased during heatwaves in 2014 and 2018.AimWe describe the epidemiology of vibriosis and the genetic diversity of Vibrio spp. isolates from Norway, Sweden, Denmark, Finland, Poland and Estonia in 2018, a year with an exceptionally warm summer.MethodsIn a retrospective study, we analysed demographics, geographical distribution, seasonality, causative species and severity of non-travel-related vibriosis cases in 2018. Data sources included surveillance systems, national laboratory notification databases and/or nationwide surveys to public health microbiology laboratories. Moreover, we performed whole genome sequencing and multilocus sequence typing of available isolates from 2014 to 2018 to map their genetic diversity.ResultsIn 2018, we identified 445 non-travel-related vibriosis cases in the study countries, considerably more than the median of 126 cases between 2014 and 2017 (range: 87-272). The main reported mode of transmission was exposure to seawater. We observed a species-specific geographical disparity of vibriosis cases across the Nordic-Baltic region. Severe vibriosis was associated with infections caused by Vibrio vulnificus (adjOR: 17.2; 95% CI: 3.3-90.5) or Vibrio parahaemolyticus (adjOR: 2.1; 95% CI: 1.0-4.5), age ≥ 65 years (65-79 years: adjOR: 3.9; 95% CI: 1.7-8.7; ≥ 80 years: adjOR: 15.5; 95% CI: 4.4-54.3) or acquiring infections during summer (adjOR: 5.1; 95% CI: 2.4-10.9). Although phylogenetic analysis revealed diversity between Vibrio spp. isolates, two V. vulnificus clusters were identified.ConclusionShared sentinel surveillance for vibriosis during summer may be valuable to monitor this emerging public health issue.
The SARS‐CoV‐2 main protease (M<sup>pro</sup>): Structure, function, and emerging therapies for COVID‐19
Authors: Qing Hu, Yuan Xiong, Guang‐Hao Zhu, Ya‐Ni Zhang, Yi‐Wen Zhang, Ping Huang, Guang‐Bo Ge
Journal: MedComm (2022)

The main proteases (M
Bacterial Toxin‐Responsive Biomimetic Nanobubbles for Precision Photodynamic Therapy against Bacterial Infections
Authors: Deli Zhuge, Li Li, Haonan Wang, Xuewei Yang, Dongyan Tian, Qingqing Yin, Hao Chen, Cuiye Weng, Bin Wen, Yijing Lin, Joo Young Huh, Xufei Zhang, Mengchun Chen, Congying Xie, Yingzheng Zhao, Yijie Chen
Journal: Advanced Healthcare Materials (2022)

Abstract With few options available for the effective treatment of multidrug‐resistant bacteria, photodynamic therapy (PDT) has emerged as a promising therapeutic strategy that does not promote the development of antibiotic resistance. Unfortunately, the beneficial bactericidal effect of PDT is oftentimes accompanied by the uncontrollable production of reactive oxygen species. To overcome this issue, a pore‐forming toxin (PFT)‐responsive biomimetic nanobubble is designed, which is constructed by co‐encapsulating a perfluorocarbon nanoemulsion and a photosensitizer within the red blood cell membrane. It is shown that PFTs derived from three pathogens, including methicillin‐resistant Staphylococcus aureus (MRSA), group A Streptococcus (GAS), and Listeria monocytogenes (LM), can be effectively absorbed by the nanobubble. Upon toxin absorption, the formation of pores on the nanobubble surface allows the accelerated release of oxygen dissolved inside the nanoemulsion along with the photosensitizer, thus resulting in enhanced PDT and bactericidal efficacy. In three skin infection models, treatment with the nanobubbles results in significantly decreased lesion formation and reduced inflammation. In addition to oxygen, the platform can be used to deliver nitric oxide in a bacterial toxin‐dependent manner. Overall, biomimetic nanobubbles may work as a broad gas delivery system that is capable of responding to a variety of PFT‐based stimuli for precision PDT.
Enhanced oral absorption of teriparatide with therapeutic potential for management of osteoporosis
Authors: Laxman Subedi, Prashant Pandey, Seo Hee Kang, Ki-Taek Kim, Seung-Sik Cho, Kwan-Young Chang, Youngro Byun, Jung-Hyun Shim, Jin Woo Park
Journal: Journal of Controlled Release (2022)
Dual-sensitive drug-loaded hydrogel system for local inhibition of post-surgical glioma recurrence
Authors: Sunhui Chen, Qiujun Qiu, Dongdong Wang, Dejun She, Bo Yin, Guolong Gu, Meihong Chai, Dong Nyoung Heo, Huining He, Jianxin Wang
Journal: Journal of Controlled Release (2022)
Lipidomic profiling in the Strong Heart Study identified American Indians at risk of chronic kidney disease
Authors: Wenjie Zeng, Habtamu B. Beyene, Mikko Kuokkanen, Guanhong Miao, Dianna J. Magliano, Jason G. Umans, Nora Franceschini, Shelley A. Cole, George Michailidis, Elisa T. Lee, Barbara V. Howard, Oliver Fiehn, Joanne E. Curran, John Blangero, Peter J. Meikle, Jinying Zhao
Journal: Kidney International (2022)
Duration of infectious shedding of SARS-CoV-2 Omicron variant and its relation with symptoms
Authors: Şiran Keske, Gülen Güney-Esken, Cansel Vatansever, Yeşim Beşli, Zeynep Ece Kuloğlu, Zeliş Nergiz, Tayfun Barlas, Özgür Şencanlı, Mert Ahmet Kuşkucu, Erhan Palaoğlu, Füsun Can, None Önder Ergönül
Journal: Clinical Microbiology and Infection (2022)
Silicate ions as soluble form of bioactive ceramics alleviate aortic aneurysm and dissection
Authors: Yumei Que, Zhaowenbin Zhang, Yanxin Zhang, Xin Li, Likai Chen, Peier Chen, Caiwen Ou, Chen Yang, Jiang Chang
Journal: Bioactive Materials (2022)

Aortic aneurysm and dissection (AAD) are leading causes of death in the elderly. Recent studies have demonstrated that silicate ions can manipulate multiple cells, especially vascular-related cells. We demonstrated in this study that silicate ions as soluble form of bioactive ceramics effectively alleviated aortic aneurysm and dissection in both Ang II and β-BAPN induced AAD models. Different from the single targeting therapeutic drug approaches, the bioactive ceramic derived approach attributes to the effect of bioactive silicate ions on the inhibition of the AAD progression through regulating the local vascular microenvironment of aorta systematically in a multi-functional way. The in vitro experiments revealed that silicate ions did not only alleviate senescence and inflammation of the mouse aortic endothelial cells, enhance M2 polarization of mouse bone marrow-derived macrophages, and reduce apoptosis of mouse aortic smooth muscle cells, but also regulate their interactions. The in vivo studies further confirm that silicate ions could effectively alleviate senescence, inflammation, and cell apoptosis of aortas, accomplished with reduced aortic dilation, collagen deposition, and elastin laminae degradation. This bioactive ceramic derived therapy provides a potential new treatment strategy in attenuating AAD progression.
HLA-B∗46 associates with rapid HIV disease progression in Asian cohorts and prominent differences in NK cell phenotype
Authors: Shuying S. Li, Andrew Hickey, Shida Shangguan, Philip K. Ehrenberg, Aviva Geretz, Lauryn Butler, Gautam Kundu, Richard Apps, Matthew Creegan, Robert J. Clifford, Suteeraporn Pinyakorn, Leigh Anne Eller, Pikunchai Luechai, Peter B. Gilbert, Timothy H. Holtz, Anupong Chitwarakorn, Carlo Sacdalan, Eugène Kroon, Nittaya Phanuphak, Mark de Souza, Jintanat Ananworanich, Robert J. O'Connell, Merlin L. Robb, Nelson L. Michael, Sandhya Vasan, Rasmi Thomas
Journal: Cell Host & Microbe (2022)

Human leukocyte antigen (HLA) alleles have been linked to HIV disease progression and attributed to differences in cytotoxic T lymphocyte (CTL) epitope representation. These findings are largely based on treatment-naive individuals of European and African ancestry. We assessed HLA associations with HIV-1 outcomes in 1,318 individuals from Thailand and found HLA-B∗46:01 (B∗46) associated with accelerated disease in three independent cohorts. B∗46 had no detectable effect on HIV-specific T cell responses, but this allele is unusual in containing an HLA-C epitope that binds inhibitory receptors on natural killer (NK) cells. Unbiased transcriptomic screens showed increased NK cell activation in people with HIV, without B∗46, and simultaneous single-cell profiling of surface proteins and transcriptomes revealed a NK cell subset primed for increased responses in the absence of B∗46. These findings support a role for NK cells in HIV pathogenesis, revealed by the unique properties of the B∗46 allele common only in Asia.
Dihydrotanshinone I preconditions myocardium against ischemic injury via PKM2 glutathionylation sensitive to ROS
Authors: Xunxun Wu, Lian Liu, Qiuling Zheng, Hui Ye, Hua Yang, Haiping Hao, Ping Li
Journal: Acta Pharmaceutica Sinica B (2022)

Ischemic preconditioning (IPC) is a potential intervention known to protect the heart against ischemia/reperfusion injury, but its role in the no-reflow phenomenon that follows reperfusion is unclear. Dihydrotanshinone I (DT) is a natural compound and this study illustrates its role in cardiac ischemic injury from the aspect of IPC. Pretreatment with DT induced modest ROS production and protected cardiomyocytes against oxygen and glucose deprivation (OGD), but the protection was prevented by a ROS scavenger. In addition, DT administration protected the heart against isoprenaline challenge. Mechanistically, PKM2 reacted to transient ROS via oxidization at Cys423/Cys424, leading to glutathionylation and nuclear translocation in dimer form. In the nucleus, PKM2 served as a co-factor to promote HIF-1α-dependent gene induction, contributing to adaptive responses. In mice subjected to permanent coronary ligation, cardiac-specific knockdown of Pkm2 blocked DT-mediated preconditioning protection, which was rescued by overexpression of wild-type Pkm2, rather than Cys423/424-mutated Pkm2. In conclusion, PKM2 is sensitive to oxidation, and subsequent glutathionylation promotes its nuclear translocation. Although IPC has been viewed as a protective means against reperfusion injury, our study reveals its potential role in protection of the heart from no-reflow ischemia.
3D Printed Biomimetic Metamaterials with Graded Porosity and Tapering Topology for Improved Cell Seeding and Bone Regeneration
Authors: Lei Zhang, Bingjin Wang, Bo Song, Yonggang Yao, Seung-Kyum Choi, Cao Yang, Yusheng Shi
Journal: Bioactive Materials (2022)

Biomimetic metallic biomaterials prepared for bone scaffolds have drawn more and more attention in recent years. However, the topological design of scaffolds is critical to cater to multi-physical requirements for efficient cell seeding and bone regeneration, yet remains a big scientific challenge owing to the coupling of mechanical and mass-transport properties in conventional scaffolds that lead to poor control towards favorable modulus and permeability combinations. Herein, inspired by the microstructure of natural sea urchin spines, biomimetic scaffolds constructed by pentamode metamaterials (PMs) with hierarchical structural tunability were additively manufactured via selective laser melting. The mechanical and mass-transport properties of scaffolds could be simultaneously tuned by the graded porosity (B/T ratio) and the tapering level (D/d ratio). Compared with traditional metallic biomaterials, our biomimetic PM scaffolds possess graded pore distribution, suitable strength, and significant improvements to cell seeding efficiency, permeability, and impact-tolerant capacity, and they also promote in vivo osteogenesis, indicating promising application for cell proliferation and bone regeneration using a structural innovation.
Trends, clinicopathological features, surgical treatment patterns and prognoses of early-onset versus late-onset colorectal cancer: A retrospective cohort study on 34067 patients managed from 2000 to 2021 in a Chinese tertiary center
Authors: Xian Hua Gao, Juan Li, Lian Jie Liu, Nan Xin Zheng, Kuo Zheng, Zubing Mei, Chen Guang Bai, Wei Zhang
Journal: International Journal of Surgery (2022)
Risk-based stratified primary care for common musculoskeletal pain presentations (STarT MSK): a cluster-randomised, controlled trial
Authors: Jonathan C Hill, Stefannie Garvin, Kieran Bromley, Benjamin Saunders, Jesse Kigozi, Vince Cooper, Martyn Lewis, Joanne Protheroe, Simon Wathall, Adrian Chudyk, Kate M Dunn, Hollie Birkinshaw, Sue Jowett, Elaine M Hay, Danielle van der Windt, Christian Mallen, Nadine E Foster
Journal: The Lancet Rheumatology (2022)
VP6-2022: Adjuvant pertuzumab and trastuzumab in patients with early HER-2 positive breast cancer in APHINITY: 8.4 years' follow-up
Authors: S. Loibl, J. Jassem, A. Sonnenblick, D. Parlier, E. Winer, J. Bergh, R.D. Gelber, E. Restuccia, Y-H. Im, C. Huang, F. Dalenc, I. Calvo, M. Procter, C. Caballero, E. Clark, H.L. Gomez Moreno, J. Bliss, G. Viale, J. Bines, M. Piccart
Journal: Annals of Oncology (2022)